PubMed Update October/November 2016

43 papers this round, and there are some goodies in here for sure (don’t miss #38!). Given the number and varied issues addressed, I divided them up into topic areas and, given the number on naloxone, I divided up the naloxone topic areas as well.

Naloxone interventions

Primary care

1) Co-prescription of naloxone as a Universal Precautions model for patients on chronic opioid therapy-Observational study.

Takeda MY, Katzman JG, Dole E, Bennett MH, Alchbli A, Duhigg D, Yonas H.

Subst Abus. 2016 Apr 19:1-6. [Epub ahead of print]

Comment: A pilot of naloxone co-prescribing.

2) Attitudes Toward Naloxone Prescribing in Clinical Settings: A Qualitative Study of Patients Prescribed High Dose Opioids for Chronic Non-Cancer Pain.

Mueller SR, Koester S, Glanz JM, Gardner EM, Binswanger IA.

J Gen Intern Med. 2016 Oct 31. [Epub ahead of print]

Comment: Shows that naloxone for patients prescribed opioids must be appropriately framed.

3) Acceptability of Naloxone Co-Prescription Among Primary Care Providers Treating Patients on Long-Term Opioid Therapy for Pain.

Behar E, Rowe C, Santos GM, Coffa D, Turner C, Santos NC, Coffin PO.

J Gen Intern Med. 2016 Nov 4. [Epub ahead of print]

Comment: When actually implemented, providers really like adding naloxone to opioid-related care. One of five papers out of the Naloxone for Opioid Safety Evaluation of a naloxone co-prescribing study in San Francisco.

Emergency department

4) Emergency Department-based Opioid Harm Reduction: Moving Physicians From Willing to Doing.

Samuels EA, Dwyer K, Mello MJ, Baird J, Kellogg AR, Bernstein E.

Acad Emerg Med. 2016 Apr;23(4):455-65. doi: 10.1111/acem.12910.

Comment: There needs to be some high-level leadership in emergency medicine before we see real movement from emergency docs.

5) Why is it so hard to implement change? A qualitative examination of barriers and facilitators to distribution of naloxone for overdose prevention in a safety net environment.

Drainoni ML, Koppelman EA, Feldman JA, Walley AY, Mitchell PM, Ellison J, Bernstein E.

BMC Res Notes. 2016 Oct 18;9(1):465.

Comment: Uptake of naloxone provision from emergency departments has been surprisingly challenging.

6) Factors Associated With Participation in an Emergency Department-Based Take-Home Naloxone Program for At-Risk Opioid Users.

Kestler A, Buxton J, Meckling G, Giesler A, Lee M, Fuller K, Quian H, Marks D, Scheuermeyer F.

Ann Emerg Med. 2016 Oct 10. pii: S0196-0644(16)30407-3. doi: 10.1016/j.annemergmed.2016.07.027. [Epub ahead of print]

Comment: If you offer it from emergency departments, you’ll get reasonable uptake. Interesting in the context of our other ED naloxone papers from this month.

Corrections

7) Randomized controlled pilot trial of naloxone-on-release to prevent post-prison opioid overdose deaths.

Parmar MK, Strang J, Choo L, Meade AM, Bird SM.

Addiction. 2016 Oct 24. doi: 10.1111/add.13668. [Epub ahead of print]

Comment: Interesting piece on the N-ALIVE trial, which was possibly our last real hope for a definitive randomized controlled trial of naloxone provision. Unfortunately it didn’t work out, but there is still room for some innovative trial designs to try to get close to such definitive data.

8) Stakeholder perceptions and operational barriers in the training and distribution of take-home naloxone within prisons in England.

Sondhi A, Ryan G, Day E.

Harm Reduct J. 2016 Feb 3;13:5. doi: 10.1186/s12954-016-0094-1.

Comment: Interesting elements of the challenges of providing naloxone in prisons, including identifying eligible inmates, inmate and staff perceptions, and logistical barriers.

Substance use treatment

9) Opioid overdose and naloxone education in a substance use disorder treatment program.

Lott DC, Rhodes J.

Am J Addict. 2016 Apr;25(3):221-6. doi: 10.1111/ajad.12364.

Comment: If you don’t give them naloxone, they don’t go get it themselves. This is like a flu vaccination. People don’t go out of their way for preventive interventions.

Distribution program

10) Process evaluation of the Prevent Overdose in Toronto (POINT) program.

Leece P, Gassanov M, Hopkins S, Marshall C, Millson P, Shahin R.

Can J Public Health. 2016 Oct 20;107(3):e224-e230. doi: 10.17269/cjph.107.5480.

Comment: As above.

Law enforcement / emergency medical service response

11) Police Officers Can Safely and Effectively Administer Intranasal Naloxone.

Fisher R, O’Donnell D, Ray B, Rusyniak D.

Prehosp Emerg Care. 2016 Nov-Dec;20(6):675-680.

Comment: A relief that few patients become combative in this situation.

12) Law Enforcement Attitudes towards Naloxone Following Opioid OverdoseTraining.

Purviance D, Ray B, Tracy A, Southard E.

Subst Abus. 2016 Aug 11:0. [Epub ahead of print]

Comment: Changes in the role of police for people who use drugs is a meaningful element of this process.

13) Implementation of online opioid overdose prevention, recognition and response trainings for professional first responders: Year 1 survey results.

Simmons J, Rajan S, Goldsamt L, Elliott L.

Drug Alcohol Depend. 2016 Oct 11;169:1-4. doi: 10.1016/j.drugalcdep.2016.10.003. [Epub ahead of print]

Comment: Evaluation of online naloxone training, with some innovative elements.

These two papers address early release by emergency medical personnel after naloxone administration.

14) Do heroin overdose patients require observation after receiving naloxone?

Willman MW, Liss DB, Schwarz ES, Mullins ME.

Clin Toxicol (Phila). 2016 Nov 16:1-7. [Epub ahead of print]

Comment: The short answer is “no”. Nice summary.

15) Is a Prehospital Treat and Release Protocol for Opioid Overdose Safe?

Kolinsky D, Keim SM, Cohn BG, Schwarz ES, Yealy DM.

J Emerg Med. 2016 Oct 18. pii: S0736-4679(16)30777-6. doi: 10.1016/j.jemermed.2016.09.015. [Epub ahead of print]

Comment: Probably per this paper. Yes per the parallel one that came out this month.

Miscellaneous

16) Can Naloxone Be Used to Treat Synthetic Cannabinoid Overdose?

Jones JD, Nolan ML, Daver R, Comer SD, Paone D.

Biol Psychiatry. 2016 Aug 18. pii: S0006-3223(16)32710-X. doi: 10.1016/j.biopsych.2016.08.013. [Epub ahead of print] No abstract available.

Comment: Interesting that naloxone seemed to help in these cases, in the absence of presence of opioids. There is an interaction between the opioid and cannabinoid receptor systems (which was actually an element of my undergraduate work with cannabinoids and pain – a theory suggested by the late J Michael Walker from Brown University).

Prescription opioids and chronic pain

17) Prescription drug abuse – A timely update.

Monheit B, Pietrzak D, Hocking S.

Aust Fam Physician. 2016 Dec;45(12):862-866.

Comment: Prescription opioids in Australia. And buprenorphine is really safe.

18) Opioid Misuse/Abuse and Quality Persistent Pain Management in Older Adults.

Chang YP, Compton P.

J Gerontol Nurs. 2016 Dec 1;42(12):21-30. doi: 10.3928/00989134-20161110-06.

Comment: Hopefully the new efforts at opioid prescribing will help. I remain concerned that, without substantial investments in funding other pain management strategies, feelings of patient abandonment will worsen.

19) Challenges to Treatment of Chronic Pain and Addiction During the “Opioid Crisis”.

Krashin D, Murinova N, Sullivan M.

Curr Pain Headache Rep. 2016 Dec;20(12):65. Review.

Comment: Per title.

20) Turning the Tide or Riptide? the Changing Opioid Epidemic.

Kertesz SG.

Subst Abus. 2016 Nov 18:0. [Epub ahead of print]

Comment: A pointed analysis of issues with the continued focus on opioid prescribing, when reforms have been followed by explosions in the use and consequences of street opioids.

21) Risk factors for opioid overdose and awareness of overdose risk among veterans prescribed chronic opioids for addiction or pain.

Wilder CM, Miller SC, Tiffany E, Winhusen T, Winstanley EL, Stein MD.

J Addict Dis. 2016;35(1):42-51. doi: 10.1080/10550887.2016.1107264.

Comment: Everybody underestimates their overdose risk. The next question is what does this mean (e.g. does this apply to most medical disorders?) and what do we do with the information?

22) Opioid Overdose: Risk Assessment and Mitigation in Outpatient Treatment.

Lin LA, Hosanagar A, Park TW, Bohnert AS.

J Addict Med. 2016 Nov/Dec;10(6):382-386.

Comment: Can’t access this case report of a patient with comorbid chronic pain and substance use disorder who had a heroin overdose.

23) Declines in Opioid Prescribing After a Private Insurer Policy Change – Massachusetts, 2011-2015.

García MC, Dodek AB, Kowalski T, Fallon J, Lee SH, Iademarco MF, Auerbach J, Bohm MK.

MMWR Morb Mortal Wkly Rep. 2016 Oct 21;65(41):1125-1131. doi: 10.15585/mmwr.mm6541a1.

Comment: Opioid stewardship interventions reduced opioid prescribing in Massachusetts. No surprise there. But no analysis of what happened to patients who were no longer prescribed opioids. We’re in the midst of a crisis and really need to go further than just looking at opioid prescribing.

24) Management of patients with issues related to opioid safety, efficacy and/or misuse: a case series from an integrated, interdisciplinary clinic.

Becker WC, Merlin JS, Manhapra A, Edens EL.

Addict Sci Clin Pract. 2016 Jan 28;11(1):3. doi: 10.1186/s13722-016-0050-0.

Comment: It takes a lot of work to manage patients well; many providers do not have the resources to pull this off.

25) Efficacy and safety of two methadone titration methods for the treatment of cancer-related pain: The EQUIMETH2 trial (methadone for cancer-related pain).

Poulain P, Berleur MP, Lefki S, Lefebvre D, Chvetzoff G, Serra E, Tremellat F, Derniaux A, Filbet M; EQUIMETH2 Study Group..

J Pain Symptom Manage. 2016 Sep 29. pii: S0885-3924(16)30312-8. doi: 10.1016/j.jpainsymman.2016.05.022. [Epub ahead of print]

Comment: Use of methadone as second-line pain control in cancer patients.

26) Factors associated with opioid overdose: a 10-year retrospective study of patients in a large integrated health care system.

Boscarino JA, Kirchner HL, Pitcavage JM, Nadipelli VR, Ronquest NA, Fitzpatrick MH, Han JJ.

Subst Abuse Rehabil. 2016 Sep 16;7:131-141.

Comment: Nice, large study, no surprising results.

27) Mandatory Provider Review And Pain Clinic Laws Reduce The Amounts Of Opioids Prescribed And Overdose Death Rates.

Dowell D, Zhang K, Noonan RK, Hockenberry JM.

Health Aff (Millwood). 2016 Oct 1;35(10):1876-1883.

Comment: Wow this is complicated. And I’m unsure that amalgamated national data can appropriately reflect the reasons for such complicated results. The real impact in terms of overdose mortality, if there is one, is from prescribed opioids. It seems a stretch to say these data show a reduction in overall opioid overdose mortality.

Toxicology reports:

28) Risk Factors for Mortality and Endotracheal Intubation after MethadoneIntoxication.

Hassanian-Moghaddam H, Soltaninejad K, Shadnia S, Kabir A, Movahedi M, Mirafzal A.

Basic Clin Pharmacol Toxicol. 2016 Mar;118(3):231-7. doi: 10.1111/bcpt.12476.

Comment: Interesting that age seemed to predict the worst outcomes in methadone overdose. Again makes me wonder about what makes older opioid users seem more likely to die of overdose while younger users overdose more frequently.

27) Non-cardiogenic pulmonary edema, rhabdomyolysis and myocardial injury following heroin inhalation: a case report.

Bazoukis G, Spiliopoulou A, Mourouzis K, Grigoropoulou P, Yalouris A.

Hippokratia. 2016 Jan-Mar;20(1):84-87.

Comment: Title says it all.

28) An Unusual Case of Alternating Ventricular Morphology on the 12-Lead Electrocardiogram.

Sammon M, Dawood A, Beaudoin S, Harrigan RA.

J Emerg Med. 2016 Oct 7. pii: S0736-4679(16)30686-2. doi: 10.1016/j.jemermed.2016.08.027. [Epub ahead of print]

Comment: An overdose reversal case that led to the diagnosis of a variant of Wolff-Parkinson White, which is a cardiac disorder that can be life threatening.

29) Clinical effects of unintentional pediatric buprenorphine exposures: experience at a single tertiary care center.

Toce MS, Burns MM, O’Donnell KA.

Clin Toxicol (Phila). 2016 Oct 19:1-6. [Epub ahead of print]

Comment: Effects are similar to other opioids for infants/toddlers, and duration of observation required is dependent upon dose.

Substance use disorder treatment

30) Striatal H3K27 Acetylation Linked to Glutamatergic Gene Dysregulation in Human Heroin Abusers Holds Promise as Therapeutic Target.

Egervari G, Landry J, Callens J, Fullard JF, Roussos P, Keller E, Hurd YL.

Biol Psychiatry. 2016 Sep 28. pii: S0006-3223(16)32833-5. doi: 10.1016/j.biopsych.2016.09.015. [Epub ahead of print]

Comment: Interesting exploration of novel interventions for opioid use disorder.

31) Fifty Years in the Development of a Glutaminergic-Dopaminergic Optimization Complex (KB220) to Balance Brain Reward Circuitry in Reward Deficiency Syndrome: A Pictorial.

Blum K, Febo M, Badgaiyan RD.

Austin Addict Sci. 2016;1(2). pii: 1006.

Comment: More on novel pharmacotherapies for opioid use disorder.

32) Treatment utilization among persons with opioid use disorder in the United States.

Wu LT, Zhu H, Swartz MS.

Drug Alcohol Depend. 2016 Oct 19;169:117-127. doi: 10.1016/j.drugalcdep.2016.10.015. [Epub ahead of print]

Comment: Yup, the United States has issues with providing appropriate treatments for opioid use disorder. These issues are multi-faceted, ranging from the unbelievable stigma faced by a person who even admits to any drug use in a medical setting, to the finance issues in a fragmented, barely hung together healthcare system slated to be further trampled in the next couple of years.

Epidemilogy / qualitative results

33) Assessing gender disparities in excess mortality of heroin or cocaine users compared to the general population.

Brugal MT, Molist G, Sarasa-Renedo A, de la Fuente L, Espelt A, Mesías B, Puerta C, Guitart AM, Barrio G; Spanish Working Group for the Study of Mortality amongDrug Users..

Int J Drug Policy. 2016 Nov 11;38:36-42. doi: 10.1016/j.drugpo.2016.10.009. [Epub ahead of print]

Comment: Gender comparison in overdose.

34) [Harm reduction interventions in drug users: current situation and recommendations].

Bosque-Prous M, Brugal MT.

Gac Sanit. 2016 Nov;30 Suppl 1:99-105. doi: 10.1016/j.gaceta.2016.04.020. Spanish.

Comment: Review of harm reduction strategies from Spain.

35) Longitudinal changes in psychological distress in a cohort of people who inject drugs in Melbourne, Australia.

Scott N, Carrotte ER, Higgs P, Cogger S, Stoové MA, Aitken CK, Dietze PM.

Drug Alcohol Depend. 2016 Nov 1;168:140-146. doi: 10.1016/j.drugalcdep.2016.08.638.

Comment: Psychological distress is a major and fascinating domain in substance use disorders.

36) Drug use in business bathrooms: An exploratory study of manager encounters in New York City.

Wolfson-Stofko B, Bennett AS, Elliott L, Curtis R.

Int J Drug Policy. 2016 Oct 18;39:69-77. doi: 10.1016/j.drugpo.2016.08.014. [Epub ahead of print]

Comment: Interesting argument for supervised injection facilities.

36) County-Level Vulnerability Assessment for Rapid Dissemination of HIV or HCV Infections Among Persons Who Inject Drugs, United States.

Van Handel MM, Rose CE, Hallisey EJ, Kolling JL, Zibbell JE, Lewis B, Bohm MK, Jones CM, Flanagan BE, Siddiqi AE, Iqbal K, Dent AL, Mermin JH, McCray E, Ward JW, Brooks JT.

J Acquir Immune Defic Syndr. 2016 Nov 1;73(3):323-331.

Comment: Great paper. Innovative approach and analysis. Kudos.

37) Performance measures of diagnostic codes for detecting opioid overdose in the emergency department.

Rowe C, Vittinghoff E, Santos GM, Behar E, Turner C, Coffin P.

Acad Emerg Med. 2016 Oct 20. doi: 10.1111/acem.13121. [Epub ahead of print]

Comment: ICD coding for opioid poisoning in a safety net hospital detected only a quarter of opioid overdose cases, suggesting that surveillance of this issue based on billing codes in emergency departments may vastly underestimate the number of cases. It is also possible that there is huge variation in how cases are coded. Unfortunately, this is another strike against using “big data” in substance use research. The reasons for poor coding are many, including stigma.

38) Risk of fentanyl overdose among clients of the Sydney Medically Supervised Injecting Centre.

Latimer J, Ling S, Flaherty I, Jauncey M, Salmon AM.

Int J Drug Policy. 2016 Oct 14;37:111-114. doi: 10.1016/j.drugpo.2016.08.004. [Epub ahead of print]

Comment: Nice work by this team! Fentanyl injection had twice the risk of overdose of heroin injection and eight times the risk of injection other prescribed opioids. Although this is observational, it’s the first data we have to start to paint the picture.

39) Communicating risk in the context of methadone formulation changes: A qualitative study of overdose warning posters in Vancouver, Canada.

Markwick N, McNeil R, Anderson S, Small W, Kerr T.

Int J Drug Policy. 2016 Jan;27:178-81. doi: 10.1016/j.drugpo.2015.10.013. No abstract available.

Comment: Warnings should emphasize the specific risks for harm, not the potency.

40) Emergence of methadone as a street drug in St. Petersburg, Russia.

Heimer R, Lyubimova A, Barbour R, Levina OS.

Int J Drug Policy. 2016 Jan;27:97-104. doi: 10.1016/j.drugpo.2015.10.001.

Comment: Methadone use has increased from 4% in 2010 to 53% in 2012/13, and its use is associated with fewer HIV risk behaviors than heroin use.

41) Do drug seizures predict drug-related emergency department presentations or arrests for drug use and possession?

Wan WY, Weatherburn D, Wardlaw G, Sarafidis V, Sara G.

Int J Drug Policy. 2016 Jan;27:74-81. doi: 10.1016/j.drugpo.2015.09.012.

Comment: Not really, in Australia at least.